Study On The Correlation Between Serum Exosomal MiR-21,MiR-122,MiR-126 And Acute Coronary Syndrome And Gensini Scores

Background:Acute coronary syndrome(ACS)can be classified into unstable angina pectoris(UA)and acute myocardial infarction(AMI),and its high incidence rate and mortality rate are its characteristics,Exosomes are membrane vesicles with a diameter of 40-100nm.There are many kinds of nucleic acids in exosomes,including messenger RNA(mRNA),microRNA(miRNA)and other non coding RNA.At present,researches on exosome miRNA as a diagnostic biomarker of cancer,stroke,diabetes and other diseases have been reported.However,although some studies have found that there are the expression of miR-133a and miR-1 increased in AMI and UA,However,the study of exosomal miRNA as a biomarker for the diagnosis of ACS has not yet been reported.It was found that serum exosomal miR-21,miR-122,miR-126 were associated with coronary endothelial injury,and the pathogenesis of ACS was also associated with vascular endothelial injury and other pathological processes.It was speculated that serum exosomal miR-21,miR-122 and miR-126 might be used as biomarkers for the diagnosis of AMI and UA.Moreover,the lipid double-layer packaging can prevent exosomes from being degraded by humoral enzymes,which makes exosomes have relatively long and stable expression time in biological fluids.Therefore,serum exosomal miR-21,miR-122 and miR-126 may be more stable biomarkers for the diagnosis of UA and AMI.After previous experiments,we found that the expression levels of serum exosomal miR-21,miR-122 and miR-126 in ACS patients were higher than those in normal controls.The Gensini score is mainly used to obtain the patient’s blood flow status through coronary angiography,and on this basis to achieve a quantitative judgment of the degree of coronary artery stenosis.The serum miRNA level and Gensini score can be used to quickly estimate the degree of coronary artery stenosis.However,the correlation between serum exosomal miRNA and Gensini score has not been publicly reported.In this study,we investigated the correlation between serum exosomal miR-21,miR-122,miR-126 as a biomarker for the diagnosis of ACS and its expression level with Gensini score,in order to find a stable biomarker that diagnoses ACS patients and assesses the severity of coronary stenosis based on Gensini scores..Methods:In this paper,the subjects were divided into three groups,including 31 in AMI group.34 included in UA group,and 22 included in control group.Healthy individuals of similar age(40-70 years)as UA and AMI were selected for the control group.Coronary angiography should be performed on the day of blood collection.Coronary stenosis in each ACS patient who met the ACS criteria was evaluated and the Gensini score was calculated.Fasting blood was collected in the UA group and the control group in the morning,and blood was collected in the AMI group after chest pain in the hospital.Serum was separated from the blood,exosomes were separated from the serum by hypervelocity centrifugation,and exosomes were identified by electron microscopy and biomarker proteins(CD9,CD63,CD81).The actual expression levels of exosomal miR-21,miR-122 and miR-126 in serum were detected by qPCR,using Prism and SPSS to analyze the data obtained.The threshold of statistical significance is set to p<0.05Results:Serum exosomal miR-21 decreased in the UA contrasted with the control group(p<0.05),the AMI group decreased significantly contrasted with the control group(p<0.001),and the AMI group showed no significant change in the expression level contrasted with the UA.Serum exosomal miR-126 increased significantly in the UA contrasted with the control group(p<0.001),the AMI group significantly increased in the control group(p<0.001),and the AMI group increased in the UA group(p<0.01).Serum exosome miR-122 increased significantly in the UA contrasted with the control group(p<0.001),the AMI group significantly increased in control group(p<0.001),and the AMI group significantly increased in the UA(p<0.001).Pearson correlation analysis showed that serum exosomal miR-21,miR-122,miR-126 was not correlated with age,sex,diastolic blood pressure,heart rate,systolic blood pressure,creatine,NT-proBNP,glucose,TG and total cholesterol.Compared with the control group,the area of serum exosomal miR-21 under the operating characteristic curve of AMI group was 0.8422(P<0.0001),and that of UA group was 0.8489(P<0.0001).The AUC of serum exosomal miR-126 in AMI group was 0.8489(P<0.001),UA group was 0.7815(P=0.0005).The AUC of serum exosomal miR-122 in AMI group was 0.924(P<0.0001),UA group was 0.765(p<0.0001).According to Gensini score,there was no correlation between serum miR-21 level and Gensini score of UA patients(r=0.1329;95%CI=-0.3427-0.3659;P=0.9425)and AMI patients(r=0.0882;95%CI=-0.2576-0.4140;P=0.6199).Serum exosomal miR-122 was positively related to Gensini score in UA(r=0.591,P=0.0002),but not with Gensini score of AMI patients(r=0.235,P=0.203).Serum exosomal miR-126 was positively related to Gensini score in UA(r=0.7137,P<0.0001)and AMI(r=0.6028,P=0.0003).Conclusion:1.Serum exosomal miR-122,miR-126 may be used as a biomarker for the diagnosis of AMI and UA.2.Serum exosomal miR-21 may be used as a diagnostic biomarker for ACS.3.Serum exosomal miR-126 may forecast stenosis of coronary artery in ACS.Elevated serum exosomal miR-122 levels may forecast stenosis of coronary artery in UA.